The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.
Journal article, 2015
Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.
genetics
Escherichia coli
metabolism
pharmacology
Humans
Base Sequence
metabolism
metabolism
Escherichia coli Proteins
metabolism
chemistry
chemistry
genetics
Amino Acid Motifs
In Vitro Techniques
Molecular Sequence Data
Protein Structure
alpha-Synuclein
Secondary
drug effects
Protein Aggregates
Amyloid beta-Peptides
Author
Margery L Evans
E. Chorell
Jonathan D Taylor
J. Åden
Anna Götheson
Fei Li
Marion Koch
Lea Sefer
Steve J Matthews
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
F. Almqvist
Matthew R Chapman
Molecular Cell
1097-2765 (ISSN) 1097-4164 (eISSN)
Vol. 57 3 445-55Subject Categories (SSIF 2011)
Cell Biology
Biochemistry and Molecular Biology
Biophysics
DOI
10.1016/j.molcel.2014.12.025
PubMed
25620560